scholarly journals Update on acute promyelocytic leukemia in the pediatric population

2021 ◽  
Vol 9 (5) ◽  
pp. 91-96
Author(s):  
Adriana Ruiz-Rodriguez ◽  
Lucia ObandoMadrigal ◽  
Ana Lucia Mateus-Vargas
Keyword(s):  
Acute Promyelocytic Leukemia ◽  
Pediatric Population ◽  
Current Treatment ◽  
Promyelocytic Leukemia ◽  
Response To Therapy ◽  
Response To Treatment ◽  
All Trans Retinoic Acid ◽  
Low Incidence ◽  
Shed Light ◽  
New Mutations

Acute promyelocytic leukemia (APL) has shown differences in incidence around the world, it has a characteristic molecular, pathogenic and clinical development mechanism. Despite being a low incidence acute myeloid leukemia (AML) compared to other AML and having a good response to therapy, it continues to be of interest due to the toxicities of its current treatment, to mutations that have shown resistance to those drugs, and to the few possibilities of alternative treatment with all-trans retinoic acid (ATRA) and anthracyclines in the pediatric population. Furthermore, the description of new mutations that originate APL produced by LPA generates new interest in studies that may shed light on their effects on the disease’s incidence, prognoses, and response to treatment. This article aims to review different studies that describe findings of APL in terms of incidences, treatments, side effects, survival, especially in the pediatric population. Different studies propose the use of ATRA - arsenic trioxide (ATO) as the first line of treatment, however, few have been carried out in the pediatric population and the use of ATO is not recommended in children under 5 years of age. On the other hand, the differentiation syndrome (DS) has been d

scholarly journals PLZF-RARα, NPM1-RARα, and Other Acute Promyelocytic Leukemia Variants: The PETHEMA Registry Experience and Systematic Literature Review

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1313 ◽  
Author(s):  
Marta Sobas ◽  
Maria Carme Talarn-Forcadell ◽  
David Martínez-Cuadrón ◽  
Lourdes Escoda ◽  
María J. García-Pérez ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Complete Remission ◽  
Acute Promyelocytic Leukemia ◽  
Fusion Gene ◽  
Retinoic Acid Receptor ◽  
Promyelocytic Leukemia ◽  
High Relapse Rate ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Shed Light

It has been suggested that 1–2% of acute promyelocytic leukemia (APL) patients present variant rearrangements of retinoic acid receptor alpha (RARα) fusion gene, with the promyelocytic leukaemia zinc finger (PLZF)/RARα being the most frequent. Resistance to all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) has been suggested in PLZF/RARα and other variant APLs. Herein, we analyze the incidence, characteristics, and outcomes of variant APLs reported to the multinational PETHEMA (Programa para el Tratamiento de Hemopatias Malignas) registry, and we perform a systematic review in order to shed light on strategies to improve management of these extremely rare diseases. Of 2895 patients with genetically confirmed APL in the PETHEMA registry, 11 had variant APL (0.4%) (9 PLZF-RARα and 2 NPM1-RARα), 9 were men, with median age of 44.6 years (3 months to 76 years), median leucocytes (WBC) 16.8 × 109/L, and frequent coagulopathy. Eight patients were treated with ATRA plus chemotherapy-based regimens, and 3 with chemotherapy-based. As compared to previous reports, complete remission and survival was slightly better in our cohort, with 73% complete remission (CR) and 73% survival despite a high relapse rate (43%). After analyzing our series and performing a comprehensive and critical review of the literature, strong recommendations on appropriate management of variant APL are not possible due to the low number and heterogeneity of patients reported so far.

scholarly journals Management of acute promyelocytic leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet

Blood ◽  
2009 ◽  
Vol 113 (9) ◽  
pp. 1875-1891 ◽  
Author(s):  
Miguel A. Sanz ◽  
David Grimwade ◽  
Martin S. Tallman ◽  
Bob Lowenberg ◽  
Pierre Fenaux ◽  
...  
Keyword(s):  
Acute Promyelocytic Leukemia ◽  
Genetic Diagnosis ◽  
Treatment Strategies ◽  
Promyelocytic Leukemia ◽  
Cytotoxic Agents ◽  
Response To Treatment ◽  
International Panel ◽  
All Trans Retinoic Acid ◽  
Disease Biology ◽  
Life Threatening

The introduction of all-trans retinoic acid (ATRA) and, more recently, arsenic trioxide (ATO) into the therapy of acute promyelocytic leukemia (APL) has revolutionized the management and outcome of this disease. Several treatment strategies using these agents, usually in combination with chemotherapy, but also without or with minimal use of cytotoxic agents, have provided excellent therapeutic results. Cure of APL patients, however, is also dependent on peculiar aspects related to the management and supportive measures that are crucial to counteract life-threatening complications associated with the disease biology and molecularly targeted treatment. The European LeukemiaNet recently appointed an international panel of experts to develop evidence- and expert opinion–based guidelines on the diagnosis and management of APL. Together with providing current indications on genetic diagnosis, modern risk-adapted front-line therapy and salvage treatment, the review contains specific recommendations for the identification and management of most important complications such as the bleeding disorder, APL differentiation syndrome, QT prolongation and other ATRA- and ATO-related toxicities, as well as for molecular assessment of response to treatment. Finally, the approach to special situations is also discussed, including management of APL in children, elderly patients, and pregnant women.

Treatment of newly diagnosed acute promyelocytic leukemia without cytarabine.

1997 ◽  
Vol 15 (2) ◽  
pp. 483-490 ◽  
Author(s):  
E Estey ◽  
P F Thall ◽  
S Pierce ◽  
H Kantarjian ◽  
M Keating
Keyword(s):  
Acute Promyelocytic Leukemia ◽  
Cox Regression ◽  
Disease Free Survival ◽  
Current Treatment ◽  
Promyelocytic Leukemia ◽  
Newly Diagnosed ◽  
Current Group ◽  
Free Survival ◽  
All Trans Retinoic Acid

PURPOSE To determine the effect of omission of cytarabine (ara-C) from treatment of newly diagnosed acute promyelocytic leukemia (APL), which allows administration of more anthracycline. PATIENTS AND METHODS Induction consisted of all-trans retinoic acid (ATRA) 45 mg/m2 daily until complete remission (CR) and idarubicin 12 mg/m2 daily for 4 days beginning on day 5 of ATRA. Patients in CR received two courses of idarubicin 12 mg/m2 daily for 3 days and then, until 2 years post-CR date, alternated three cycles of mercaptopurine, vincristine, methotrexate, and prednisone (POMP) with one cycle of idarubicin 12 mg/m2 daily for 2 days. Results in the 43 patients treated (41 with t(15;17) on standard or Southern analysis) were compared with those in 57 historic newly diagnosed APL patients given ara-C with either doxorubicin, amsacrine (AMSA), or daunorubicin without ATRA, using logistic and Cox regression to assess effects of non-treatment-related covariates on patient outcomes. RESULTS The CR rate in the current group was 77% (95% confidence interval [CI], 62% to 88%) and was not significantly different from the historic rate. In contrast, disease-free survival (DFS) in CR is superior in the current group (probability at 1 year 0.87; 95% CI, 0.73 to 1.0). This has translated into superior overall DFS for the current group (P = .03 adjusting for the predictive covariates initial WBC and platelet count; 1-year DFS probability 0.67; 95% CI, 0.52 to 0.82; median follow-up 102 weeks). The current treatment appears better both in patients with and without t(15; 17) on standard cytogenetic analysis. CONCLUSION Given the difficulties inherent in comparing sequential studies and recognizing the multiple differences in treatment between current and historic groups, our results suggest that a large randomized trial incorporating use of ATRA should assess the utility of omitting ara-C from treatment of newly diagnosed APL, thus allowing delivery of more anthracycline.

The unique aspects of acute promyelocytic leukemia.

1990 ◽  
Vol 8 (11) ◽  
pp. 1913-1921 ◽  
Author(s):  
R M Stone ◽  
R J Mayer
Keyword(s):  
Acute Promyelocytic Leukemia ◽  
Antigen Expression ◽  
Promyelocytic Leukemia ◽  
Disseminated Intravascular Coagulopathy ◽  
Distinctive Features ◽  
All Trans Retinoic Acid ◽  
Hla Dr ◽  
Intravascular Coagulopathy ◽  
Stimulating Factor ◽  
Shed Light

Acute promyelocytic leukemia (APL) accounts for approximately 10% of cases of acute myeloid leukemia (AML). Distinctive features of this disorder at the time of diagnosis include leukopenia coexisting with a marrow replaced with granulated dysplastic promyelocytes, disseminated intravascular coagulopathy, lack of Ia (HLA-DR) antigen expression, and translocation between the long arms of chromosomes 15 and 17 (t[15;17]). Heparin is widely but not universally used to interfere with the coagulopathy during the initial phases of treatment. Serial bone marrow examinations during the induction period demonstrate the achievement of remission despite the persistence of malignant-appearing promyelocytes. Patients with APL are generally younger than those with other subtypes of AML, have a 70% to 80% likelihood of entering remission, and are thought to have a more favorable prognosis than other individuals with AML. Remission may be achieved with a conventional anthracycline-cytarabine combination, anthracycline alone, or, apparently, all-trans retinoic acid. Genes potentially important in myeloid differentiation such as granulocyte colony-stimulating factor (G-CSF) and myeloperoxidase are located close to the breakpoint in the t(15;17) but have not been conclusively shown to be rearranged in the translocation. A better understanding of the unique aspects of APL may well shed light on the pathogenetic processes of AML.

scholarly journals Acute Promyelocytic Leukemia in Pediatric Population: A Rare Presentation

2020 ◽  
Vol 5 (2) ◽  
pp. 83-85
Author(s):  
Rabiah Asghar ◽  
◽  
Javera Tariq ◽  
Shahzad Ali Jiskani ◽  
Sundas Ali ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Retinoic Acid ◽  
Acute Promyelocytic Leukemia ◽  
Pediatric Population ◽  
Promyelocytic Leukemia ◽  
Rare Presentation ◽  
Term Survival ◽  
Sudan Black B ◽  
All Trans Retinoic Acid ◽  
Appropriate Therapy

Abstract: Acute Promyelocytic Leukemia (APL) is a very uncommon type of acute myeloid leukemiacomprising less than 10% of pediatric population. Acute Promyelocytic leukemia is a neoplastic proliferation of abnormal promyelocytes in bone marrow, caused by cytogenetic abnormality t(15;17). Majority of patients (80%) have long term survival, and death occurs in approximately 10% of patients in early course of the disease; mainly because of hemorrhage. Hemorrhagic complications can be reduced by appropriate therapy if started timely, which ultimately reduces the risk of death.We report a case of 7 years old boy with complaints of fever off and on for past 06 months, bruises and swelling on left leg for 1 week, blood containing vomiting for 1day. He was diagnosed as APL on bone marrow biopsy. Keywords: Acute promyelocytic leukemia, Paediatric, Retinoic acid syndrome, All-Trans retinoic acid, FAB AML-M3, Sudan Black-B.

scholarly journals Management of acute promyelocytic leukemia: updated recommendations from an expert panel of the European LeukemiaNet

Blood ◽  
2019 ◽  
Vol 133 (15) ◽  
pp. 1630-1643 ◽  
Author(s):  
Miguel A. Sanz ◽  
Pierre Fenaux ◽  
Martin S. Tallman ◽  
Elihu H. Estey ◽  
Bob Löwenberg ◽  
...  
Keyword(s):  
Acute Promyelocytic Leukemia ◽  
Expert Panel ◽  
Genetic Diagnosis ◽  
Early Death ◽  
Promyelocytic Leukemia ◽  
Response To Treatment ◽  
All Trans Retinoic Acid ◽  
High Risk Disease ◽  
Frontline Therapy

Abstract Since the comprehensive recommendations for the management of acute promyelocytic leukemia (APL) reported in 2009, several studies have provided important insights, particularly regarding the role of arsenic trioxide (ATO) in frontline therapy. Ten years later, a European LeukemiaNet expert panel has reviewed the recent advances in the management of APL in both frontline and relapse settings in order to develop updated evidence- and expert opinion–based recommendations on the management of this disease. Together with providing current indications on genetic diagnosis, modern risk-adapted frontline therapy, and salvage treatment, the review contains specific recommendations for the identification and management of the most important complications such as the bleeding disorder APL differentiation syndrome, QT prolongation, and other all-trans retinoic acid– and ATO-related toxicities, as well as recommendations for molecular assessment of the response to treatment. Finally, the approach to special situations is also discussed, including management of APL in children, elderly patients, and pregnant women. The most important challenges remaining in APL include early death, which still occurs before and during induction therapy, and optimizing treatment in patients with high-risk disease.

scholarly journals Prolonged Myelosuppression due to Progressive Bone Marrow Fibrosis in a Patient with Acute Promyelocytic Leukemia

2019 ◽  
Vol 2019 ◽  
pp. 1-7
Author(s):  
Yuta Inagawa ◽  
Yukiko Komeno ◽  
Satoshi Saito ◽  
Yuji Maenohara ◽  
Tetsuro Yamagishi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Promyelocytic Leukemia ◽  
Bone Marrow Biopsy ◽  
Gastric Fluid ◽  
Promyelocytic Leukemia ◽  
Consolidation Therapy ◽  
Bone Marrow Fibrosis ◽  
All Trans Retinoic Acid ◽  
Phlegmonous Gastritis ◽  
Marrow Fibrosis

A 34-year-old woman was diagnosed with acute promyelocytic leukemia. Chemotherapy was administered following the JALSG APL204 protocol. Induction therapy with all-trans retinoic acid resulted in complete remission on day 49. She developed coccygeal pain from day 18, which spread to the spine and cheekbones and lasted 5 weeks. She had similar bone pain on days 7–10 of the first consolidation therapy and on days 4–12 of the second consolidation therapy. Oral loxoprofen was prescribed for pain relief. On day 33 of the third consolidation, white blood cell and neutrophil counts were 320/μL and 20/μL, respectively. After she developed epigastralgia and hematemesis, she developed septic shock. Gastroendoscopy revealed markedly thickened folds and diffusely damaged mucosa with blood oozing. Computed tomography revealed thickened walls of the antrum and the pylorus. Despite emergency treatments, she died. Bacterial culture of the gastric fluid yielded Enterobacter cloacae and enterococci growth. Collectively, she was diagnosed with phlegmonous gastritis. Retrospective examination of serial bone marrow biopsy specimens demonstrated progressive bone marrow fibrosis, which may have caused prolonged myelosuppression. Thus, evaluation of bone marrow fibrosis by bone marrow biopsy after each treatment cycle might serve as a predictor of persistent myelosuppression induced by chemotherapy.

Hypercalcemia associated with the interaction between all trans retinoic acid and posaconazole in an acute promyelocytic leukemia case

2021 ◽  
pp. 107815522110078
Author(s):  
Hacer Berna Afacan Ozturk ◽  
Murat Albayrak ◽  
Senem Maral ◽  
Merih Reis Aras ◽  
Fatma Yilmaz ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Acute Promyelocytic Leukemia ◽  
Serum Calcium ◽  
Promyelocytic Leukemia ◽  
Cytochrome P450 Enzymes ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Normal Ranges ◽  
Rare Side Effect ◽  
High Level

Introduction All-trans retinoic acid (ATRA) is a physiological metabolite of vitamin A and it is used for the treatment of acute promyelocytic leukemia (APL). Hypercalcemia is a rare side effect of ATRA and it may be potentiated after interaction of ATRA with azole group antifungals. Herein, we have reported an APL case with hypercalcemia that is caused by the interaction of ATRA and posaconazole. Case Report A 49-year-old female patient was diagnosed as APL after the examinations performed upon the detection of pancytopenia when she had presented with the complaints of widespread bruising and fever. After the initiation of posaconazole and ATRA, her serum calcium levels begin to increase (10.3 to 11.1mg/dl). Her vitamin D level was 21.9 ng/ml and PTH 17.8 pg/ml, both were in the normal ranges. The Drug Interaction Probability Scale score of our case was calculated as 6, indicating that the probable adverse drug reaction. Therefore, the high level of serum calcium was attributed to the interaction between ATRA and posaconazole. Management & Outcome Although hypercalcemia with ATRA and other antifungal agents have been previously reported in the literature, this is the first report of hypercalcemia with the concomitant use of ATRA and posaconazole. Discussion This case highlights the importance of monitoring ATRA’s side effects when it is used in combination with drugs inhibiting the cytochrome P450 enzymes. In conclusion, the concomitant use of posaconazole and ATRA may lead to hypercalcemia and serum calcium levels return to normal ranges with the discontinuation of these drugs.

In vitro all-trans retinoic acid sensitivity of acute promyelocytic leukemia blasts: a novel indicator of poor patient outcome

Blood ◽  
2001 ◽  
Vol 98 (9) ◽  
pp. 2862-2864 ◽  
Author(s):  
Bruno Cassinat ◽  
Sylvie Chevret ◽  
Fabien Zassadowski ◽  
Nicole Balitrand ◽  
Isabelle Guillemot ◽  
...  
Keyword(s):  
Acute Promyelocytic Leukemia ◽  
Promyelocytic Leukemia ◽  
Leukemic Cells ◽  
Event Free Survival ◽  
Free Survival ◽  
Acid Sensitivity ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

Abstract Acute promyelocytic leukemia (APL) blasts possess a unique sensitivity to the differentiating effects of all-transretinoic acid (ATRA). Multicenter trials confirm that the combination of differentiation and cytotoxic therapy prolongs survival in APL patients. However relapses still occur, and exquisite adaptation of therapy to prognostic factors is essential to aim at a possible cure of the disease. A heterogeneity was previously reported in the differentiation rate of patients' APL blasts, and it was postulated that this may reflect the in vivo heterogeneous outcome. In this study, it is demonstrated that patients of the APL93 trial whose leukemic cells achieved optimal differentiation with ATRA in vitro at diagnosis had a significantly improved event-free survival (P = .01) and lower relapse rate (P = .04). This analysis highlights the importance of the differentiation step in APL therapy and justifies ongoing studies aimed at identifying novel RA-differentiation enhancers.

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